The role of trace reactive gases in regulating complex biological processes such as vasorelaxation and neurotransmission has received considerable attention in the biomedical research community, including the 1998 Nobel Prize in Medicine for research on the physiological significance of NO in biological processes. Research on the role of gases such as NO and CO requires improvements in reliable, rapid, and continuous monitors of gas production in the pmol/min range. In the proposed effort, Physical Sciences Inc. (PSI) and Rice University will combine their extensive background in trace gas detection to develop the first such sensor for continuous monitoring of biologically-produced trace gases. The sensor will be based on room-temperature, Quantum Cascade mid-IR laser sources and an ultra-sensitive balanced detection technique with projected detection limits for NO and CO in the ppb range. The Phase I portion of the program will demonstrate ultra- sensitive detection of both gases in representative biomedical applications. In the Phase II portion of the program, this data will be used to design prototype instruments. Extensive collaboration with biomedical research laboratories will allow beta testing and optimization of commercial units. PROPOSED COMMERCIAL APPLICATIONS: A versatile gas analyzer for rapid and continuous measurements of trace gases in biomedical research applications is expected to generate markets of 50 to 100 units/year. Potentially larger markets exist for monitoring trace gases in breath. Beyond these medical markets, extensive industrial markets are projected for mid-IR laser-based sensors. PSI has previously developed and spun-off commercial subsidiaries for addressing medical and chemical process monitoring applications. This experience will be drawn upon in the instrument design, engineering for manufacturability, software, and marketing strategies developed for the proposed sensor.